{"id":13855,"date":"2025-10-14T11:47:03","date_gmt":"2025-10-14T04:47:03","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=13855"},"modified":"2025-10-14T11:47:03","modified_gmt":"2025-10-14T04:47:03","slug":"gabapentin","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/gabapentin\/","title":{"rendered":"Gabapentin"},"content":{"rendered":"

(Ph. Eur. monograph 2173)<\/p>\n

C9<\/sub>H17<\/sub>NO2<\/sub>\u00a0 \u00a0 \u00a0 171.2\u00a0 \u00a0 \u00a0 \u00a0 60142-96-3<\/p>\n

Action and use<\/strong><\/p>\n

Antiepileptic.<\/p>\n

Preparations<\/strong><\/p>\n

Gabapentin Capsules<\/p>\n

Gabapentin Oral Solution<\/p>\n

Gabapentin Tablets<\/p>\n

DEFINITION<\/h2>\n[1-(Aminomethyl)cyclohexyl]acetic acid.<\/p>\n

Content<\/h3>\n

97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

White or almost white, crystalline powder.<\/p>\n

Solubility<\/h3>\n

Sparingly soluble in water, slightly soluble in ethanol (96 per cent), practically insoluble in methylene chloride. It dissolves in dilute acids and dilute solutions of alkali hydroxides.
\nIt shows polymorphism (5.9).<\/p>\n

IDENTIFICATION<\/h2>\n

Infrared absorption spectrophotometry (2.2.24).<\/p>\n

Comparison: gabapentin CRS.<\/p>\n

If the spectra obtained show differences, dissolve the substance to be examined and the reference substance separately in methanol R, evaporate to dryness and record new spectra using the residues.<\/p>\n

TESTS<\/h2>\n

Appearance of solution<\/h3>\n

The solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n

Dissolve 1.50 g in a mixture of 0.5 mL of acetic acid R, 19.5 mL of methanol R and 30 mL of water R.<\/p>\n

pH (2.2.3)<\/h4>\n

6.5 to 7.5.<\/p>\n

Dissolve 1.0 g in carbon dioxide-free water R and dilute to 50 mL with the same solvent.<\/p>\n

Related substances<\/h3>\n

A. Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n

Solution A: Dissolve 2.32 g of ammonium dihydrogen phosphate R in 950 mL of water R, adjust to pH 2.0 with phosphoric acid R, and dilute to 1000 mL with water R.
\nBuffer solution Dissolve 0.58 g of ammonium dihydrogen phosphate R and 1.83 g of sodium perchlorate R in 950 mL of water for chromatography R, adjust to pH 1.8 with perchloric acid R, and dilute to 1000 mL with water for chromatography R.<\/p>\n

Test solution: Dissolve 0.140 g of the substance to be examined in solution A and dilute to 10.0 mL with solution A.<\/p>\n

Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with solution A. Dilute 1.0 mL of this solution to 10.0 mL with solution A.<\/p>\n

Reference solution (b): Dissolve 7.0 mg of gabapentin impurity A CRS and 10 mg of gabapentin impurity B CRS in methanol R1 and dilute to 50.0 mL with the same solvent. Dilute 1.0 mL of the solution to 10.0 mL with solution A.<\/p>\n

Reference solution (c): Dissolve 0.140 g of gabapentin CRS in solution A and dilute to 10.0 mL with solution A.<\/p>\n

Reference solution (d): Dissolve 7.0 mg of gabapentin impurity D CRS in 25 mL of methanol R1 and dilute to 100.0 mL with solution A. Dilute 1.0 mL of this solution to 10.0 mL with solution A.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n

\u2014 stationary phase: end-capped ethylene-bridged octadecylsilyl silica gel for chromatography (hybrid material) R (5 \u03bcm);<\/p>\n

\u2014 temperature: 40 \u00b0C.<\/p>\n

Mobile phase: acetonitrile R1, buffer solution (24:76 V\/V).<\/p>\n

Flow rate: 1.0 mL\/min.<\/p>\n

Detection: Spectrophotometer at 215 nm.<\/p>\n

Injection: 20 \u03bcL of the test solution and reference solutions (a) and (b).<\/p>\n

Run time: 4 times the retention time of gabapentin.<\/p>\n

Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A and B.<\/p>\n

Relative retention: With reference to gabapentin (retention time = about 4 min): impurity A = about 2.4; impurity B = about 2.8.<\/p>\n

System suitability: Reference solution (b):<\/p>\n

\u2014 resolution: minimum 2.3 between the peaks due to impurities A and B.<\/p>\n

To avoid memory effects between 2 chromatograms, the column may be washed using acetonitrile R1.<\/p>\n

Limits:<\/p>\n

\u2014 impurity A: not more than 1.5 times the area of the corresponding peak in the chromatogram obtained with reference solution (b) (0.15 per cent);<\/p>\n

\u2014 unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);<\/p>\n

\u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n

The thresholds indicated under Related substances (Table 2034.-1) in the general monograph Substances for pharmaceutical use (2034) do not apply for this test.<\/p>\n

B. Liquid chromatography (2.2.29) as described in test A for related substances with the following modifications.<\/p>\n

Mobile phase: methanol R2, acetonitrile R1, buffer solution (30:35:35 V\/V\/V).<\/p>\n

Injection: 20 \u03bcL of the test solution and reference solution (d).<\/p>\n

Run time: 1.2 times the retention time of impurity D.<\/p>\n

Retention time: Impurity D = about 10 min.<\/p>\n

Limits:<\/p>\n

\u2014 unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (d) (0.05 per cent);<\/p>\n

\u2014 disregard limit: 0.6 times the area of the principal peak in the chromatogram obtained with reference solution (d) (0.03 per cent); disregard any peak with a relative retention of not more than 0.4 with reference to impurity D.<\/p>\n

Limit:<\/p>\n

\u2014 total for tests A and B: maximum 0.5 per cent.<\/p>\n

Chlorides<\/h3>\n

Maximum 100 ppm.<\/p>\n

Dissolve 1.5 g in a mixture of 0.5 mL of acetic acid R, 19.5 mL of methanol R and 30 mL of water R. Titrate with 0.001 M silver nitrate, determining the end-point potentiometrically (2.2.20).<\/p>\n

1 mL of 0.001 M silver nitrate is equivalent to 0.03545 mg of chlorides.<\/p>\n

Water (2.5.32)<\/h4>\n

Maximum 0.3 per cent, determined on 1.000 g.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n

Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\n

Liquid chromatography (2.2.29) as described in test A for related substances with the following modification.<\/p>\n

Injection 20 \u03bcL of the test solution and reference solution (c).<\/p>\n

System suitability Reference solution (c):<\/p>\n

\u2014 symmetry factor: maximum 5.0 for the peak due to gabapentin.<\/p>\n

Calculate the percentage content of C9<\/sub>H17<\/sub>NO2<\/sub> taking into account the assigned content of gabapentin CRS.<\/p>\n

IMPURITIES<\/h2>\n

Test A for related substances<\/h3>\n

A, B, E, G.<\/p>\n

Test B for related substances<\/h3>\n

D.<\/p>\n

Specified impurities: A.<\/p>\n

Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities and\/or by the general monograph<\/p>\n

Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) B, D, E, G.<\/p>\n

\"Gabapentin\"<\/p>\n

A. 2-azaspiro[4.5]decan-3-one,<\/p>\n

\"Gabapentin\"<\/p>\n

B. (1-cyanocyclohexyl)acetic acid,<\/p>\n

\"Gabapentin\"<\/p>\n

D. [1-[(3-oxo-2-azaspiro[4.5]dec-2-yl)methyl]cyclohexyl]acetic acid,<\/p>\n

\"Gabapentin\"<\/p>\n

E. 1-(carboxymethyl)cyclohexanecarboxylic acid,<\/p>\n

\"Gabapentin\"<\/p>\n

G. [1-(2-aminoethyl)cyclohexyl]acetic acid.<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 2173) C9H17NO2\u00a0 \u00a0 \u00a0 171.2\u00a0 \u00a0 \u00a0 \u00a0 60142-96-3 Action and use Antiepileptic. Preparations Gabapentin Capsules Gabapentin Oral Solution Gabapentin Tablets DEFINITION [1-(Aminomethyl)cyclohexyl]acetic acid. Content 97.5 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, crystalline powder. Solubility Sparingly soluble in water, slightly soluble in ethanol (96…<\/p>\n","protected":false},"author":2,"featured_media":13887,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-13855","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicinal-substances"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/13855","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=13855"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/13855\/revisions"}],"predecessor-version":[{"id":13893,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/13855\/revisions\/13893"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/13887"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=13855"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=13855"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=13855"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}